Benzodiazepine Use and Neuropsychiatric Outcomes in the ICU: A Systematic Review.

OBJECTIVES: A systematic assessment of the role of benzodiazepine use during ICU stay as a risk factor for neuropsychiatric outcomes during and after ICU admission. DATA SOURCES: PubMed/Medline, EMBASE, The Cochrane Library, CINAHL, and PsychINFO. STUDY SELECTION: Databases were searched independently by two reviewers for studies in adult (former) ICU patients, reporting benzodiazepine use, and neuropsychiatric outcomes of delirium, posttraumatic stress disorder, depression, anxiety, and cognitive dysfunction. DATA EXTRACTION: Data were extracted using a piloted extraction form; methodological quality of eligible studies was assessed by applying the Quality Index checklist. DATA SYNTHESIS: Forty-nine of 3,066 unique studies identified were included. Thirty-five studies reported on neuropsychiatric outcome during hospitalization, 12 after discharge, and two at both time points. Twenty-four studies identified benzodiazepine use as a risk factor for delirium, whereas seven studies on delirium or related outcomes did not; six studies reported mixed findings. Studies with high methodological quality generally found benzodiazepine use to be a risk factor for the development of delirium. Five studies reported an association between benzodiazepine use and symptoms of posttraumatic stress disorder, depression, anxiety, and cognitive dysfunction after ICU admission; five studies reported mixed findings, and in four studies, no association was found. No association was found with methodological quality and sample size for these findings. Meta-analysis was not feasible due to major differences in study methods. CONCLUSIONS: The majority of included studies indicated that benzodiazepine use in the ICU is associated with delirium, symptoms of posttraumatic stress disorder, anxiety, depression, and cognitive dysfunction. Future well-designed studies and randomized controlled trials are necessary to rule out confounding by indication.

The Effect of Dexamethasone on Symptoms of Posttraumatic Stress Disorder and Depression After Cardiac Surgery and Intensive Care Admission: Longitudinal Follow-Up of a Randomized Controlled Trial.

OBJECTIVE: Cardiac surgery and postoperative admission to the ICU may lead to posttraumatic stress disorder and depression. Perioperatively administered corticosteroids potentially alter the risk of development of these psychiatric conditions, by affecting the hypothalamic-pituitary-adrenal axis. However, findings of previous studies are inconsistent. We aimed to assess the effect of a single dose of dexamethasone compared with placebo on symptoms of posttraumatic stress disorder and depression and health-related quality of life after cardiac surgery and ICU admission. DESIGN: Follow-up study of a randomized clinical trial. SETTING: Five Dutch heart centers. PATIENTS: Cardiac surgery patients (n = 1,244) who participated in the Dexamethasone for Cardiac Surgery trial. INTERVENTIONS: A single intraoperative IV dose of dexamethasone or placebo was administered in a randomized, double-blind way. MEASUREMENTS AND MAIN RESULTS: Symptoms of posttraumatic stress disorder, depression, and health-related quality of life were assessed with validated questionnaires 1.5 years after randomization. Data were available for 1,125 patients (90.4%); of which 561 patients received dexamethasone and 564 patients received placebo. Overall, the prevalence of psychopathology was not influenced by dexamethasone. Posttraumatic stress disorder and depression were present in, respectively, 52 patients (9.3%) and 69 patients (12.3%) who received dexamethasone and in 66 patients (11.7%) and 78 patients (13.8%) who received placebo (posttraumatic stress disorder: odds ratio, 0.82; 95% CI, 0.55-1.20; p = 0.30; depression: odds ratio, 0.92; 95% CI, 0.64-1.31; p = 0.63). Subgroup analysis revealed a lower prevalence of posttraumatic stress disorder (odds ratio, 0.23; 95% CI, 0.07-0.72; p < 0.01) and depression (odds ratio, 0.29; 95% CI, 0.11-0.77; p < 0.01) in female patients after dexamethasone administration. Health-related quality of life did not differ between groups and was not associated with psychopathology. CONCLUSIONS: Overall, our findings suggest that exogenous administration of the glucocorticoid receptor agonist dexamethasone-compared with placebo-during cardiac surgery does not positively or negatively affect the prevalence of posttraumatic stress disorder and depression. However, in female patients, beneficial effects on the occurrence of posttraumatic stress disorder and depression may be present.

Long-Term Mental Health Problems After Delirium in the ICU.

OBJECTIVES: To determine whether delirium during ICU stay is associated with long-term mental health problems defined as symptoms of anxiety, depression, and posttraumatic stress disorder. DESIGN: Prospective cohort study. SETTING: Survey study, 1 year after discharge from a medical-surgical ICU in the Netherlands. PATIENTS: One-year ICU survivors of an ICU admission lasting more than 48 hours, without a neurologic disorder or other condition that would impede delirium assessment during ICU stay. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One year after discharge, ICU survivors received a survey containing the Hospital Anxiety and Depression Scale with a subscale for symptoms of depression and a subscale for symptoms of anxiety, and the Impact of Event Scale 15 item measuring symptoms of posttraumatic stress disorder. Participants were classified as having experienced no delirium (n = 270; 48%), a single day of delirium (n = 86; 15%), or multiple days of delirium (n = 211; 37%) during ICU stay. Log-binomial regression was used to assess the association between delirium and symptoms of anxiety, depression, and posttraumatic stress disorder. The study population consisted of 567 subjects; of whom 246 subjects (43%) reported symptoms of anxiety (Hospital Anxiety and Depression Scale with a subscale for anxiety, ≥ 8), and 254 (45%) symptoms of depression (Hospital Anxiety and Depression Scale with a subscale for depression, ≥ 8). In 220 patients (39%), the Impact of Event Scale 15 item was greater than or equal to 35, indicating a high probability of posttraumatic stress disorder. There was substantial overlap between these mental health problems-63% of the subjects who scored positive for the presence of any three of the mental health problems, scored positive for all three. No association was observed between either a single day or multiple days of delirium and symptoms of anxiety, depression, or posttraumatic stress disorder. CONCLUSIONS: Although symptoms of anxiety, depression, and posttraumatic stress disorder were found to be common 1 year after critical illness, the occurrence of delirium during ICU stay did not increase the risk of these long-term mental health problems.

Feasibility of a virtual reality intervention in the intensive care unit.

BACKGROUND: Delirium prevention requires optimal management of pain and anxiety. Given the limitations of current pharmacologic interventions, evaluation of novel non-pharmacological interventions is required. Virtual reality (VR) stimulation may be a promising intervention because of its capability to reduce psychophysiological stress, pain, and anxiety and to restore cognitive and attentional capacities. OBJECTIVE: To ascertain patients' and providers' perceptions of acceptability and safety of VR intervention in the intensive care unit (ICU). METHODS: We enrolled a cohort of 15 ICU patients and 21 health care providers to administer a 15-minute session showing a relaxing beach scene with VR headsets and nature sound effects. Participants were then asked to rate their experiences on a Likert scale survey. RESULTS: The majority of patients (86%, 12 of 14) rated the headsets as moderately to very comfortable. All had moderate or greater sense of presence in the virtual environment, and 79% (11 of 14) rated their overall experience at 3 or greater (5 indicating that they enjoyed it very much). Seventy-one percent (10 of 14) of the patients felt that their anxiety was better with VR, and 57% (8 of 14) did not notice a change in their pain or discomfort. All health care providers found the headset to be at least moderately comfortable and felt a moderate or greater sense of presence. All providers concluded that VR therapy should be available for their patients. Both groups experienced minimal side effects. CONCLUSION: In this prospective study of perceptions of VR therapy for ICU patients and health care providers, there was a high level of acceptance, with minimal side effects, for both groups despite their low levels of prior experience with virtual reality and video gaming.

Neuropsychiatric outcome in subgroups of Intensive Care Unit survivors: Implications for after-care.

PURPOSE: Poor neuropsychiatric outcomes are common in survivors of critical illness but it is unclear what patient groups to target for interventions to improve mental health. We compared anxiety, depression, and post-traumatic stress disorder (PTSD) symptoms and health-related quality of life (HrQoL) across different subgroups of Intensive Care Unit (ICU) survivors. MATERIALS AND METHODS: A single-center cohort study was conducted in a mixed-ICU in the Netherlands among survivors of an ICU admission ≥48 h (n = 1730). Survivors received a survey one year after discharge, containing the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES/IES-R), and EQ-5D (response rate of 67%). Neuropsychiatric symptoms and quality of life were evaluated in a priori defined subgroups, by chi-square tests and Mann-Whitney U tests. RESULTS: Symptoms of anxiety (HADS anxiety ≥8), depression (HADS depression ≥8), and PTSD (IES ≥35; IES-R ≥ 1.6) were reported by 34%, 33%, and 19% of ICU survivors, with a median HrQoL utility score of 0.81 (IQR:0.65-1.00). These figures were similar for survivors of ARDS, sepsis, severe multiple organ failure (SOFA>11), or ICU stay ≥7 days. CONCLUSIONS: This underlines the importance of prevention and treatment for neuropsychiatric symptoms in ICU survivors in general, not only in specific patient groups.

Genetic variation in the glucocorticoid receptor and psychopathology after dexamethasone administration in cardiac surgery patients.

The glucocorticoid receptor (GR) agonist dexamethasone is frequently used for its anti-inflammatory properties. We recently showed that a single high-dose of dexamethasone had long-lasting protective effects on the development of psychopathology after cardiac surgery and postoperative intensive care unit stay. In this study, we investigated whether common genetic variation in the hypothalamic-pituitary-adrenal (HPA)-axis would influence the susceptibility for PTSD and depression after dexamethasone administration. Participants (n = 996) of the Dexamethasone for Cardiac Surgery (DECS) randomized clinical trial were followed after receiving a single high intraoperative dose of dexamethasone (1 mg/kg), a GR agonist, or placebo. PTSD and depressive symptoms were assessed up to four years after cardiac surgery. We focused primarily on five common single nucleotide polymorphisms (SNPs) in the glucocorticoid receptor (GR). Secondarily, we comprehensively assessed common genetic variation in the FK506 binding protein (FKBP5) and the mineralocorticoid receptor (MR). The protective effects of dexamethasone on postoperative PTSD symptoms were dependent on the GR polymorphisms rs41423247 (p = .009), rs10052957 (p = .003), and rs6189 (p = .002), but not on rs6195 (p = .025) or rs6198, (p = .026) after Bonferroni correction. No genotype-dependent effects were found for postoperative depressive symptoms. Also, no associations of FKBP5 and MR polymorphisms were found on PTSD and depression outcomes. Protective effects of dexamethasone on PTSD symptoms after cardiac surgery and ICU stay seem to depend on common genetic variation in its target receptor, the GR. These effects indicate that pre-operative genetic screening could potentially help in stratifying patients for their vulnerability for developing PTSD symptoms after surgery.

[Long-term outcomes of ICU treatment]. / Langetermijnuitkomsten van IC-behandeling.

Patients admitted to an intensive care unit (ICU) comprise of a heterogeneous population with substantial differences in admission diagnosis, length of stay and co-morbidity. Therefore, very often the prognosis for each patient differs. In the Netherlands, over 20% of the more than 80,000 patients treated in ICU annually will die within a year of admission. Some of those who survive and are discharged from ICU experience persistent physical, mental and cognitive health problems post-discharge; this is called post-intensive care syndrome (PICS). One year following discharge, circa 50% of patients continue to report physical symptoms, including muscle weakness and walking difficulties. Approximately one in five patients discharged from ICU will develop symptoms akin to post-traumatic stress disorder, and one third will experience depressive symptoms for some time. It remains unclear to what extent the actual ICU admission may potentially contribute to the decline in performance status and quality of life.

Trait anxiety mediates the effect of stress exposure on post-traumatic stress disorder and depression risk in cardiac surgery patients.

BACKGROUND: Post-traumatic stress disorder (PTSD) and depression are common after cardiac surgery. Lifetime stress exposure and personality traits may influence the development of these psychiatric conditions. METHODS: Self-reported rates of PTSD and depression and potential determinants (i.e., trait anxiety and stress exposure) were established 1.5 to 4 years after cardiac surgery. Data was available for 1125 out of 1244 (90.4%) participants. Multivariable linear regressions were conducted to investigate mediating and/or moderating effects of trait anxiety on the relationship between stress exposure, and PTSD and depression. Pre-planned subgroup analyses were performed for both sexes. RESULTS: PTSD and depression symptoms were present in 10.2% and 13.1% of the participants, respectively. Trait anxiety was a full mediator of the association between stress exposure and depression in both the total cohort and female and male subgroups. Moreover, trait anxiety partially mediated the relationship between stress exposure and PTSD in the full cohort and the male subgroup, whereas trait anxiety fully mediated this relationship in female patients. Trait anxiety did not play a moderating role in the total patient sample, nor after stratification on gender. LIMITATIONS: The unequal distribution of male (78%) and female patients (22%) might limit the generalizability of our findings. Furthermore, risk factors were investigated retrospectively and with variable follow-up time. CONCLUSIONS: In cardiac surgery patients, trait anxiety was found to be an important mediator of postoperative PTSD and depression. Prospective research is necessary to verify whether these factors are reliable screening measures of individuals' vulnerability for psychopathology development after cardiac surgery.